Company Statements Archive - Page 2 of 6

MSD to Acquire Caraway Therapeutics, Inc.

Acquisition underscores MSD’s ongoing commitment to developing treatments for neurodegenerative diseases

RAHWAY, N.J., and CAMBRIDGE, Mass., November 21, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA) (NYSE: MRK), and Caraway Therapeutics, Inc. announced today that the companies have entered into a definitive agreement under which MSD, through a subsidiary, will acquire Caraway Therapeutics for a total potential consideration of up to $610 million, including an undisclosed upfront payment as well as contingent milestone payments. The upfront payment will be expensed by MSD in the fourth quarter of 2023 and included in non-GAAP results.

“Caraway’s multidisciplinary approach has yielded important progress in evaluating novel mechanisms of modulation of lysosomal function with potential for the treatment of progressive neurodegenerative diseases,” said George Addona, senior vice president, discovery, preclinical development and translational medicine, MSD Research Laboratories. “We look forward to applying our expertise to build upon this work with the goal of developing much needed disease-modifying therapies for these conditions.”

Caraway is a preclinical biopharmaceutical company pursuing innovative approaches for the treatment of genetically defined neurodegenerative and rare diseases. The company has built a pipeline of novel, small-molecule therapeutics for the treatment of genetically defined neurodegenerative and rare diseases.

“This important milestone is a testament to the hard work and dedication of the Caraway team and our mission to develop therapeutics with the potential to alter the progression of devasting neurodegenerative diseases and help patients,” said Martin D. Williams, chief executive officer, Caraway Therapeutics. “This acquisition leverages MSD’s industry-leading research and development capabilities to help further advance our discovery and preclinical programs. We thank and appreciate our investors, including SV Health Investors and its Dementia Discovery Fund, AbbVie Ventures, Amgen Ventures, Eisai Innovation and MRL Ventures Fund, for their support.”

Under the terms of the agreement, MSD, through a subsidiary, will acquire all outstanding shares of Caraway with earnout milestones associated with the development of certain pipeline candidates. The Board of Directors of Caraway Therapeutics has approved the transaction. MSD, through its MRL Ventures Fund, has been a shareholder of Caraway Therapeutics since 2018.

About Caraway Therapeutics

Caraway Therapeutics is a biopharmaceutical company pursuing novel approaches for the treatment of genetically defined neurodegenerative and rare diseases. The company is a leader in the cutting-edge science of activating cellular recycling processes to clear toxic materials and defective cellular components by modulating lysosomal function. Caraway is utilizing its unique product engine to develop proprietary insights into lysosomal function and small molecule ion channel modulation and advance a robust pipeline of precision therapeutic candidates with disease-modifying potential for patients. The company is backed by top-tier investors, including SV Health Investors and its Dementia Discovery Fund, AbbVie Ventures, MRL Ventures Fund, Amgen Ventures, and Eisai Innovation. Caraway is based in Cambridge, MA. For more information, please visit www.carawaytx.com.

About MSD

At MSD, known as Merck & Co., Inc., Rahway, N.J., USA in the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.msd.com and connect with us on Twitter, LinkedIn and YouTube.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2022 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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MSD Investor Contact:

Peter Dannenbaum (908) 447-6900

MSD Media Contacts:

Justine Moore (347) 281-3754

Olivia Finucane 00 / + 44 7881 262476

Caraway Media Contact:

Carolyn Noyes CNoyes@macdougall.bio

MSD Presents New Analyses Supporting the Promising Potential of Sotatercept, its Investigational Medicine for Adults with Pulmonary Arterial Hypertension (PAH)

Exploratory post-hoc analysis of STELLAR shows potential of sotatercept to improve cardiovascular function

Interim results from SOTERIA open-label extension study represent longest safety and efficacy analysis of sotatercept to date; safety profile of sotatercept consistent with previous studies and efficacy improvements maintained after one year of therapy

Nine MSD-sponsored abstracts in PAH featured at European Respiratory Society (ERS) International Congress 2023

RAHWAY, N.J., Aug 25, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA) (NYSE: MRK), today announced new analyses from studies of sotatercept, MSD’s novel investigational activin signaling inhibitor biologic, for adults with pulmonary arterial hypertension (PAH) (WHO Group 1) at the European Respiratory Society (ERS) International Congress 2023. A new exploratory post-hoc analysis of right heart catheterization and echocardiography data from patients in the Phase 3 STELLAR study showed treatment with sotatercept for 24 weeks on top of background therapy reduced right heart size and improved right-ventricular (RV) function and hemodynamic status. This analysis was featured in an oral presentation, with simultaneous publication in the European Respiratory Journal. An interim analysis of the Phase 3 SOTERIA open-label extension study was also presented, representing the longest safety and efficacy analysis of sotatercept to date.

“There is an urgent need for new approaches to manage PAH, a rare, progressive, and ultimately life-threatening disease,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, MSD Research Laboratories. “These latest data build on the clinically meaningful efficacy results from the STELLAR trial and support our belief that sotatercept has the potential to transform the treatment of PAH. PAH can strain the heart and lead to eventual right heart failure, so we are particularly encouraged by the exploratory analysis from STELLAR suggesting that treatment with sotatercept improved right heart size and function.”

Primary efficacy results from STELLAR, in which sotatercept on top of background therapy demonstrated a statistically significant and clinically meaningful improvement in 6-minute walk distance (6MWD) at 24 weeks and eight of nine secondary outcome measures, were presented at ACC .2 3/WCC and published in The New England Journal of Medicine. MSD submitted an application for regulatory approval of sotatercept to the U.S. Food and Drug Administration and plans to submit applications to additional regulatory agencies worldwide.

At ERS 2023, nine MSD-sponsored studies in PAH were presented. These include an oral presentation of a population health model predicting the long-term impact of sotatercept on morbidity and mortality in patients with PAH (#OA740).

Results from STELLAR hemodynamics and echocardiography analysis (Abstract #3111)

An exploratory post-hoc analysis from the STELLAR trial evaluated the effects of sotatercept on select hemodynamic parameters and right-ventricle (RV) function. The STELLAR trial enrolled 323 adults with PAH, randomized to receive sotatercept (n=163) or placebo (n=160), on top of background therapy. Participants with available data at screening and week 24 visits were included in this post-hoc analysis, which reported hemodynamic data from 298 participants and echocardiography data from 275 participants, representing 92% and 85% of total participants respectively. In the analysis, after 24 weeks, sotatercept was associated with meaningful improvements in certain measures of hemodynamic status and RV function.

Results from this exploratory analysis showed treatment with sotatercept compared to placebo, on top of background therapy, led to improvements from baseline in mean pulmonary arterial (PA) pressure (−13.9 mmHg), PA compliance (0.58 mL mmHg⁻¹), pulmonary vascular resistance (−254.8 dyn·s·cm⁻⁵), mean right atrial pressure (−2.7 mmHg), mixed venous oxygen saturation (3.84%), PA elastance (−0.42 mmHg mL⁻¹ beat⁻¹), cardiac efficiency (0.48 mL beat⁻¹ mmHg⁻¹), RV work (−0.85 g·m) and RV power (−32.70 mmHg·L min⁻¹). Echocardiography data showed improvements in the ratio of tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP; 0.12 mm mmHg⁻¹), end-systolic and end-diastolic RV areas (−4.39 cm² and −5.31 cm², respectively), tricuspid regurgitation and RV fractional area change (2.04% p<0.050). No significant between-group changes from baseline were seen for TAPSE, heart rate, cardiac output/index or stroke volume/stroke volume index.

“Despite available therapies, PAH remains incurable, with high morbidity and mortality, highlighting the urgent need for novel treatments that target new pathways,” said Dr. Vallerie McLaughlin*, professor of medicine and director, Pulmonary Hypertension Program, Division of Cardiovascular Medicine, University of Michigan in Ann Arbor. “Sotatercept is the first activin signaling inhibitor therapy and is proposed to modulate the vascular proliferation underlying PAH. Acknowledging the exploratory nature of these findings, this is the first clinical evidence suggesting that sotatercept may positively impact certain measures of right heart function and dimensions. This is encouraging and further supports the primary results from the STELLAR analysis, underscoring the potential of sotatercept to play a critical role in the treatment of PAH.”

Results from SOTERIA study (Abstract #OA739)

SOTERIA (NCT04796337) is an ongoing open-label extension study evaluating the long-term safety, tolerability and efficacy of sotatercept when added to background therapy for the treatment of PAH in patients who have completed previous sotatercept studies without early discontinuation. The primary objective of SOTERIA is to evaluate long-term safety and tolerability. The secondary objective is to assess the continued efficacy of sotatercept, as measured by 6MWD, N-terminal pro-B-type natriuretic peptide (NT-proBNP), WHO functional class (FC), pulmonary vascular resistance, overall survival, and simplified French risk score.

“The SOTERIA study provides us with important insight into the longer-term safety and efficacy of sotatercept,” said Dr. Ioana Preston, director of the Pulmonary Hypertension Center and associate professor at Tufts University School of Medicine. “These results support the potential durability of clinical benefit and safety of sotatercept for the treatment of PAH.”

At the data cutoff of April 20, 2023, there were 409 participants enrolled in SOTERIA. All participants were evaluated for safety. The median duration of exposure to sotatercept was 462 days (range: 21-1,762 days), including any exposure to sotatercept during the parent study. One hundred forty-three participants rolled over from placebo. The median duration of exposure to sotatercept in SOTERIA was 189 days.

Sotatercept was well-tolerated and the safety profile was similar to previous studies. 98.5% of participants were on treatment at the time of the interim analysis. Treatment-emergent adverse events (TEAEs) occurred in 81.7% (n=334/409) of participants. Serious TEAEs occurred in 19.3% of participants but only a small proportion lead to treatment discontinuation (1.5%; n=6/409) or death (1.0%; n=4/409). Additionally, 22.7% (n=93/409) of participants experienced a telangiectasia event, 0% had a serious telangiectasia event, 0% discontinued treatment and 1% experienced dose reductions or holds due to telangiectasia. Clinical worsening events were documented. Seven participants (1.7%) experienced nine clinical worsening events.

Improvements in clinical efficacy measures measured at week 24 in SOTERIA were maintained at one year during the open-label period. One hundred thirty-one participants who reached one year of therapy in SOTERIA were evaluated for efficacy at one year; most of these participants rolled over from the Phase 2 sotatercept studies, PULSAR and SPECTRA trials. Mean change (SD) from baseline at week 24 in 6MWD (20.2 ±66.5 m) and NT-proBNP (−374.9 ±1479.4 pg/mL) were largely maintained at one year (10.9 ±73.6 m and −227.2 ±1580.1 pg/mL, respectively). The proportion of participants who improved or maintained WHO FC II from baseline at week 24 (77.2%) was similar to that at one year (76.3%). 30.1% of participants achieved low French risk score (WHO-FC I/II, 6MWD >440 m, NT-proBNP <300 pg/mL) at week 24, and 37.4% at one year.

Changes in background PAH therapy were also documented for all participants. Of participants on any prostacyclin, 29/272 (10.7%) had prostacyclin dose decreases. Of participants on infusion prostacyclin, 22/154 (14.3%) had prostacyclin dose decreases. Of participants on other PAH therapy, 21/406 (5.2%) had other PAH therapy dose decreases and 19/406 (4.6%) had other PAH therapy dose increased. As of April 20, 2023, 8 participants had discontinued prostacyclins entirely.

Summary of Presentations

MSD-sponsored studies and analyses for PAH, sotatercept and MK-5475, an investigational inhaled soluble guanylate cyclase (sGC) stimulator, featured at ERS International Congress 2023 include:

Clinical studies

Effects of Sotatercept on Haemodynamics and Right Heart Function: Analysis of STELLAR Trial; Marius M. Hoeper; Abstract #3111
Sotatercept for the Treatment of PAH: An Update; Marius M. Hoeper; Abstract #807
Late Breaking Abstract – A Long-Term Follow-Up (LTFU) Study of Sotatercept for Pulmonary Arterial Hypertension (PAH); Ioana R. Preston; Abstract #807
A Randomized Study to Evaluate the Effects of Single-Dose MK-5475 Co-Administered with Sildenafil on Systemic Hemodynamics; Mahesh J. Patel; Abstract #PA1208

Population Health and Real-World Evidence

Vallerie McLaughlin; Abstract #OA740

Concordance between physician and patient reported presence of symptoms in patients with pulmonary arterial hypertension in the US, Europe and Japan; Rogier Klok; Abstract #PA3966
Diagnosing pulmonary arterial hypertension in the Real World; Rogier Klok; Abstract #PA1190
End-of-life healthcare resource utilization and costs in patients with PAH: a real-world analysis; Dominik Lautsch; Abstract #PA1195
Health related quality of life in pulmonary arterial hypertension in the US, Europe and Japan; Rogier Klok; Abstract #PA3969

*Dr. McLaughlin is an investigator in the STELLAR trial and a paid consultant to MSD.

About pulmonary arterial hypertension (PAH)

PAH is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%.

About sotatercept

Sotatercept is an investigational, potential first-in-class activin signaling inhibitor biologic being studied for the treatment of PAH (WHO Group 1). PAH is a rare disease caused by hyperproliferation of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. In pre-clinical models, sotatercept has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.

In addition to STELLAR and SOTERIA, the sotatercept clinical development program includes multiple Phase 2 and 3 trials across a broad range of patients. Studies are underway in adult patients with PAH (WHO Group 1) at intermediate or high risk of disease progression or mortality, as well as with pulmonary hypertension due to left heart disease (WHO Group 2).

MSD acquired exclusive rights to sotatercept in the pulmonary hypertension field through the acquisition of Acceleron Pharma Inc. Sotatercept is the subject of a licensing agreement with Bristol Myers Squibb.

About MK-5475

MK-5475 is an investigational dry-powder formulation of a small-molecule stimulator of soluble guanylate cyclase (sGC), designed for inhaled delivery to the pulmonary arterial circulation through the lungs. MK-5475 may stimulate sGC in the blood vessels of the lungs, which, if occurring, relaxes and widens these blood vessels. It is currently being studied in a Phase 2/3 trial for the treatment of PAH and a Phase 2 trial for the treatment of PH associated with chronic obstructive pulmonary disease.

MSD’s Focus on Cardiovascular Disease

MSD has a long history of developing treatments for cardiovascular disease. More than 60 years ago, we introduced our first cardiovascular therapy – and our scientific efforts to understand and treat cardiovascular-related disorders have continued. Cardiovascular disease continues to be one of the most serious health challenges of the 21st century. Approximately 18 million people across the globe die every year, and in the United States, one person dies every 36 seconds from cardiovascular disease.

Advancements in the treatment of cardiovascular disease can make a critical difference for patients and health systems around the world. At MSD, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally.

Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.msdclinicaltrials.com/

About MSD

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

Media Contacts:

Julie Cunningham

(617) 519-6264

Ayn Wisler

(917) 691-6218

Investor Contacts:

Peter Dannenbaum

(732) 594-1579

Damini Chokshi

(732) 594-1577

MSD Initiates Phase 3 Clinical Program for Oral PCSK9 Inhibitor Candidate MK-0616

Program plans to enroll approximately 17,000 participants across three global studies

RAHWAY, N.J., Aug 25, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA) (NYSE: MRK), today announced the initiation of the company’s Phase 3 clinical program, CORALreef, for MK-0616, an investigational, oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, being evaluated for the treatment of adults with hypercholesterolemia. This is the first Phase 3 clinical program for an oral PCSK9 inhibitor. The first participants are now enrolling in two registrational Phase 3 studies evaluating low-density lipoprotein (LDL) cholesterol reduction: CORALreef Lipids and CORALreef HeFH. MSD also plans to initiate a Phase 3 cardiovascular outcomes study, CORALreef Outcomes by the end of 2023.

PCSK9 is a validated target for lowering LDL cholesterol. However, there are no oral PCSK9 inhibitors available to physicians and patients. The Phase 3 CORALreef program follows robust Phase 2b results presented at ACC.23/WCC, in which MK-0616 significantly reduced LDL cholesterol compared to placebo at all doses studied in participants with hypercholesterolemia with a broad spectrum of atherosclerotic cardiovascular disease (ASCVD) risk, including participants on high-intensity statin therapy. MK-0616 was generally well-tolerated.

“Elevated LDL cholesterol is a major risk factor for cardiovascular disease, the leading cause of death worldwide. Despite several well-established lipid-lowering therapies, millions of people globally do not achieve and maintain their desired LDL cholesterol treatment goals, leaving them at risk for cardiac events,” said Dr. Marc Sabatine, Chair of the Thrombolysis in Myocardial Infarction (TIMI) Study Group, the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, and a Professor of Medicine at Harvard Medical School. “MK-0616 showed statistically significant LDL cholesterol lowering activity in the Phase 2 trial and has the unique aspect of being a once daily pill. With its novel modality among PCSK9 inhibitors, MK-0616 could provide an important option for patients for the treatment of hypercholesterolemia.”

“The initiation of a comprehensive Phase 3 program is an important milestone in our goal to offer a highly effective oral medication that could be accessed by a broad population and potentially allow substantially more people to reach their LDL treatment goals,” said Dr. Joerg Koglin, senior vice president, global clinical development, MSD Research Laboratories. “In acknowledgment of the significant racial, ethnic and gender disparities in cardiovascular care, MSD is taking proactive measures to engage potential participants from populations that have historically been underrepresented in clinical trials of this type.”

CORALreef Lipids (NCT05952856) is a randomized, double-blind study enrolling a broad group of participants, including participants with history of at least one major ASCVD event and those at intermediate to high risk for a first event. Participants must be treated with stable lipid lowering therapies, including at least a moderate or high intensity statin, or have documented statin intolerance. The primary objective of this study is to evaluate the efficacy of MK-0616 compared with placebo on the mean percent change from baseline in LDL cholesterol at Week 24. Participants will receive 20 mg of MK-0616 orally once daily for up to 52 weeks or placebo, on top of their background lipid lowering therapies.

CORALreef HeFH (NCT05952869) is a similar study, focused on adult participants with heterozygous familial hypercholesterolemia, who are being treated with stable lipid lowering therapies, including at least a moderate or high intensity statin. The estimated primary completion date for CORALreef Lipids and CORALreef HeFH studies is September 2025.

CORALreef Outcomes (TIMI 77) (NCT06008756) is a randomized, double-blind study in adult participants with high cardiovascular risk, who are being treated with stable lipid lowering therapies, including at least a moderate or high intensity statin. The primary objective is to evaluate the efficacy of MK-0616 compared with placebo, on top of background lipid lowering therapies, in increasing the time to the first occurrence of one of the following events: coronary heart disease death, ischemic stroke, myocardial infarction, acute limb ischemia or major amputation, or urgent arterial revascularization. MSD is collaborating with the TIMI Study Group, a leading academic research organization for cardiovascular clinical trials, on the CORALreef Outcomes study. The estimated primary completion date is November 2029.

MSD’s broad, global Phase 3 program for MK-0616 aims to enroll approximately 17,000 participants across the CORALreef Lipids, CORALreef HeFH and CORALreef Outcomes studies.

About PCSK9 and MK-0616

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 prevents the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

MK-0616 is an investigational, potentially first oral PCSK9 inhibitor designed to lower LDL cholesterol via the same biological mechanism as currently approved injectable PCSK9 inhibitors but in a daily pill form. MK-0616 is a macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

About Hypercholesterolemia

Hypercholesterolemia, a disorder in which there are elevated LDL cholesterol levels in the blood, affects approximately 86 million adults in the U.S., with nearly 25 million having very high total cholesterol above 240 mg/dL. It is a major risk factor associated with ASCVD, which is the leading cause of death in the U.S. and globally. Despite adjusting diet and taking statin therapies, many patients with hypercholesterolemia are still not reaching, or maintaining, their LDL cholesterol lowering goals as recommended by guidelines. High LDL cholesterol, if left untreated, can lead to a high risk of ASCVD events, such as heart attacks and strokes.

MSD’s Focus on Cardiovascular Disease

Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.msdclinicaltrials.com/

About MSD

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

Media Contacts:

Julie Cunningham

(617) 519-6264

Ayn Wisler

(917) 691-6218

Investor Contacts:

Peter Dannenbaum

(908) 740-1037

Damini Chokshi

(908) 740-1807

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MSD Reports Strong Progress on its Commitments to Advancing Access to Health and Operating Responsibly

Reached more than 500 million people with its innovations across commercial channels, clinical trials, access strategies, voluntary licensing and its donations in 2022
Expanded two of its Access to Health goals
Added sustainability metrics tied to its Access to Health and Employees focus areas in its 2023 Company Scorecard, which impacts annual incentive pay for executives and the majority of global employees
Committed to Science Based Targets initiative (SBTi) to set net-zero target for greenhouse gas (GHG) emissions across global operations (Scopes 1, 2 and 3)
Allocated $760 million of the net proceeds from its $1 billion sustainability bond to social and green projects, in alignment with its sustainability financing framework, through June 2022

RAHWAY, N.J., August 10, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK), has published its Impact Report 2022/2023, outlining sustained momentum and strong performance across the company’s four sustainability areas: Access to Health, Employees, Environmental Sustainability and Ethics & Values.

“The positive impact we continue to have on patients, communities and society is a direct result of our commitment to innovation and the principles and values that shape our company,” said Robert M. Davis, chairman and chief executive officer, MSD. “At our core, we believe in operating responsibly, putting patients first and raising the bar on scientific excellence. This unwavering commitment enables us to deliver value to all our stakeholders as we work with speed and urgency to save and improve lives around the world.”

Importantly, MSD has exceeded and expanded two of its Access to Health goals:

Two years ago, MSD set a goal to enable 100 million more people to access its innovative portfolio¹ globally, through access strategies, solutions and partnerships, by 2025. The company exceeded this goal already in 2022. As a result, the company increased its ambition and more than tripled the original goal. MSD now aims to enable 350 million more people to access its innovative portfolio by 2025.
Through 2022, MSD reached more than 33 million people in low-and middle-income countries (LMICs) and underserved populations in the U.S. with its social investments, exceeding its goal to reach more than 30 million people by 2025. The company’s expanded goal is to reach over 50 million people in LMICs, underserved populations in the U.S. and, going forward, underserved populations in other high-income countries, by 2025.

Additional key highlights from this year’s report include:

Access to Health

In 2022, MSD reached more than 500 million people with its innovations across commercial channels, clinical trials, access strategies, voluntary licensing and its donations.
- This includes nearly 360 million people reached through the MECTIZAN® Donation Program to treat river blindness and lymphatic filariasis².
In 2022, the company invested $38 million to advance health equity and initiatives, including MSD for Mothers, in support of its goal to reach over 30 million people with its social investments.
Through 2022, MSD’s multi-faceted strategy to facilitate timely and equitable access to its investigational antiviral COVID-19 medicine has led to the delivery of more than 5 million courses of generic COVID-19 therapy to over 20 LMICs.
- In addition, the company’s direct supply has treated more than 4 million patients worldwide through 2022.
Through a long-term agreement with UNICEF from 2021–2025, MSD has committed to provide more than 100 million doses of its human papillomavirus (HPV) vaccine for use in Gavi-supported countries.

Employees

MSD achieved greater than 99 percent pay equity in the U.S. for female and male employees, as well as for non-white (including Black, Hispanic and Asian employees) and white employees.
In 2022, 47 percent of the company’s new hires in the U.S. were members of underrepresented ethnic groups.

Environmental Sustainability

The company committed to the Science Based Targets Initiative (SBTi) to set a net-zero target for GHG emissions across its global operations (Scopes 1, 2 and 3).
In 2022, the company sourced 45 percent of its purchased electricity from renewable sources.

Ethics & Values

The company increased its spend with diverse Tier 1 and 2 suppliers globally from $2.9 billion in 2021 to $3.2 billion in 2022.

The company is utilizing the net proceeds from the sustainability bond offering to support projects and partnerships in its priority sustainability areas and to contribute to the advancement of the United Nations Sustainable Development Goals. Through June 2022 (the most recent reporting period for the bond), MSD has allocated $760 million of the net proceeds toward social and green projects, in alignment with its sustainability financing framework.

MSD also added sustainability metrics tied to its Access to Health and Employees focus areas in its 2023 Company Scorecard, which impacts annual incentive pay for executives and the majority of global employees.

Learn more about MSD’s approach to sustainability, the company’s commitment to creating value for society and all its stakeholders, and its progress on key goals in MSD’s Impact Report 2022/2023.

About MSD

At MSD, known as Merck & Co., Inc., Rahway, N.J., USA in the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.msd.com and connect with us on Twitter, LinkedIn, and YouTube.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties 10 materialize, actual results may differ materially from those set forth in the forward-looking statements.

¹ “Innovative portfolio” of products refers to our Company’s on-patent products.

² Countries receiving donated Mectizan are located in Africa, Asia, the Middle East, South America, and the Western Pacific

Media Contact:
mediarelations@msd.com

Investor Contact:
Peter Dannenbaum – (732) 594-1579

Steve Graziano – (732) 594-1583

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MSD Receives Positive European Union CHMP Opinion for Gefapixant

RAHWAY, N.J., July 21, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK), today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of gefapixant, an investigational, non-narcotic, oral selective P2X3 receptor antagonist, developed for the treatment for adults with refractory or unexplained chronic cough. The CHMP’s recommendation will now be reviewed by the European Commission (EC) for marketing authorization in the European Union (EU) and a final decision is expected later this year.

“Today’s positive CHMP opinion is the next step for gefapixant to become the first treatment approved in the European Union for adults with refractory or unexplained chronic cough,” said Dr. Joerg Koglin, senior vice president, global clinical development, MSD Research Laboratories. “Refractory or unexplained chronic cough as a condition with often disruptive, uncontrolled coughing associated with major physical, social and emotional consequences represents a large unmet clinical need.”

The CHMP’s positive opinion is based on results from the COUGH-1 and COUGH-2 clinical trials, which are the first companion Phase 3 studies ever completed in patients with refractory or unexplained chronic cough, a cough that persists despite appropriate treatment of underlying conditions or for which the underlying cause cannot be identified despite a thorough evaluation. Both studies met the primary endpoint, demonstrating a statistically significant reduction in 24-hour cough frequency in adults treated with gefapixant 45 mg twice daily versus placebo at 12 weeks (COUGH-1) and 24 weeks (COUGH-2).

About the COUGH-1 and COUGH-2 trials

COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are Phase 3 multinational, randomized, double-blind, placebo-controlled studies that evaluated the efficacy and safety of gefapixant in reducing cough frequency in adult participants with refractory chronic cough (RCC) or unexplained chronic cough (UCC). A total of 2,044 participants were treated in COUGH-1 (n=730) and COUGH-2 (n=1,314). In both studies, patients were randomly selected to receive one of the following: gefapixant 45 mg twice daily, gefapixant 15 mg twice daily, or placebo. The primary efficacy outcomes for COUGH-1 and COUGH-2 were 24-hour cough frequency at week 12 and 24-hour cough frequency at week 24, respectively, measured using an ambulatory digital audio recording device. Secondary endpoints included awake cough frequency and percentage of participants with a greater than 1.3-point increase from baseline in the Leicester Cough Questionnaire (LCQ) total score. COUGH-1 had a 12-week treatment period and a 40-week safety-extension period, while COUGH-2 had a 24-week treatment period and a 28-week safety-extension period.

In these studies, adults treated with gefapixant 45 mg twice daily demonstrated a statistically significant reduction in 24-hour cough frequency (measured objectively, as coughs per hour, using 24-hour sound recordings) versus placebo at 12 weeks (COUGH-1) (18.45% reduction relative to placebo, 95% CI [-32.92, -0.9; p=0.041]) and 24 weeks (COUGH-2) (14.64% reduction relative to placebo, 95% CI [-26.01, -1.4; p=0.031]). The gefapixant 15 mg twice daily treatment arms did not meet the primary efficacy endpoint in either Phase 3 study. The Phase 3 study results were published in The Lancet.

In 2022, MSD announced that additional analyses were underway to address questions received from regulatory authorities. The questions were primarily related to the cough counting system used in generating the Phase 3 data, on which the marketing authorization application for gefapixant was based. The results of the additional analyses were generally consistent with the published Phase 3 results from COUGH-1 and COUGH-2.

About gefapixant

Gefapixant is an investigational, orally administered, selective P2X3 receptor antagonist, for the potential treatment of refractory or unexplained chronic cough. P2X3 receptors are one of the receptor types found on sensory nerve fibers, predominantly C fibers, in the airway lining. Chemical stimuli, including adenosine triphosphate (ATP), can be released from airway lining cells due to airway inflammation, irritation, and mechanical stress/injury. Binding of extracellular ATP to P2X3 receptors on C fibers in the airway can be sensed as a signal of potential damage, creating an action potential, which may initiate coughing. The inhibition of binding of extracellular ATP to P2X3 receptors is thought to reduce sensory nerve activation and, subsequently, cough.

In 2022, gefapixant under the brand name LYFNUA^®, was approved in Japan and Switzerland for treatment of adults with refractory or unexplained chronic cough.

About chronic cough

The prevalence of chronic cough (a cough lasting more than 8 weeks) is estimated to be approximately 5 to 10% of adults globally. In a subset of these cases, patients either do not respond to treatment of underlying conditions (such as asthma or gastroesophageal reflux), known as refractory chronic cough (RCC), or they have no identifiable underlying condition despite a thorough evaluation, known as unexplained chronic cough (UCC). In the EU, there are currently no approved therapies for the treatment of RCC or UCC.

About MSD

At MSD, known as Merck & Co., Inc., Rahway, N.J., USA in in the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.msd.com and connect with us on Twitter, LinkedIn, and YouTube.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties 10 materialize, actual results may differ materially from those set forth in the forward-looking statements.

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MSD Completes Acquisition of Prometheus Biosciences, Inc.

Acquisition delivers industry-leading research capability, and strengthens pipeline with a novel candidate for ulcerative colitis, Crohn’s disease and other autoimmune conditions

RAHWAY, N.J. — MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK)) today announced the completion of the Prometheus Biosciences, Inc. (“Prometheus”) (NASDAQ: RXDX) acquisition. Prometheus is now a wholly-owned subsidiary of MSD and the common stock of Prometheus will no longer be listed or traded on the Nasdaq Global Market.

“The Prometheus acquisition accelerates our growing presence in immunology, augments our diverse pipeline and increases our ability to deliver patient value. This transaction is another example of MSD acting strategically and decisively when science and value align,” said Robert M. Davis, chairman and chief executive officer, MSD. “Prometheus brings us a potential best-in-class candidate that creates an opportunity for us to transform treatment for patients with immune-mediated diseases. We are excited to welcome our Prometheus colleagues to MSD and we look forward to working together, driven by our common purpose of saving and improving lives.”

Prometheus’ leading clinical candidate, PRA-023, which will be known as MK-7240, is a humanized monoclonal antibody (mAb) directed to tumor necrosis factor (TNF)-like ligand 1A (TL1A), a target associated with both intestinal inflammation and fibrosis. It is being developed for the treatment of immune-mediated diseases, including ulcerative colitis (UC), Crohn’s disease (CD) and other autoimmune conditions. In December 2022, Prometheus announced positive results for MK-7240 from ARTEMIS-UC, a Phase 2, placebo-controlled study evaluating safety and efficacy in patients with moderate-to-severely active UC and APOLLO-CD, and a Phase 2A, open-label study evaluating safety and efficacy in patients with moderate-to-severe CD. The findings were recently presented at the 18th Congress of European Crohn’s and Colitis Organisation (ECCO).

“At MSD we have deep expertise in clinical development with a proven record of implementing precision medicine strategies,” said Dr. Dean Y. Li, president of MSD Research Laboratories. “By combining our strengths, MSD and Prometheus are well positioned to advance MK-7240 and additional pipeline candidates.”

Additional Transaction Details

Under the terms of the acquisition agreement, MSD, through a subsidiary, has acquired all outstanding shares of Prometheus for $200.00 per share in cash for a total equity value of approximately $10.8 billion. MSD’s full-year financial outlook provided during the first-quarter earnings call did not account for the then proposed acquisition of Prometheus or any additional significant potential business development transactions.

As previously disclosed, because this transaction is being accounted for as an asset acquisition, MSD is recording a charge of approximately $10.3 billion, or approximately $4.00 per share. The impact of this charge will result in a reduction in both second-quarter and full-year 2023 GAAP and non-GAAP results. In addition, this transaction is expected to negatively impact EPS by approximately $0.25 in the first 12 months following the close of the transaction due to investment to advance pipeline assets and cost of financing, approximately half of which will be incurred in the second half of 2023.

As a matter of policy, MSD provides updates to its financial outlook once each quarter. When considering MSD’s financial outlook issued on April 27, 2023, investors and analysts should deduct the expenses outlined above. MSD will provide an update to its financial outlook when it reports second quarter 2023 results on August 1.

About Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a term used to collectively describe Crohn’s disease and ulcerative colitis. These conditions are characterized by chronic inflammation of the gastrointestinal (GI) tract. Prolonged inflammation results in damage to the tissues lining the GI tract. Both ulcerative colitis and Crohn’s disease are usually characterized by diarrhea, rectal bleeding, abdominal pain, fatigue and weight loss.

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MSD’s Investigational Activin Signaling Inhibitor Sotatercept Improved Six-Minute Walk Distance by 40.8 Meters at Week 24 Versus Placebo in Adults with Pulmonary Arterial Hypertension on Background Therapy

Sotatercept demonstrated statistically significant improvements in 8 of 9 secondary measures, including reduction in risk of clinical worsening or death

Results presented today at ACC.23/WCC and published in The New England Journal of Medicine

RAHWAY, N.J., March 6, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK) today announced full results from the Phase 3 STELLAR trial, which evaluated sotatercept, MSD’s novel investigational activin signaling inhibitor biologic, in combination with stable background therapy for the treatment of adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1). Sotatercept significantly improved exercise capacity, increasing 6-minute walk distance (6MWD) by 40.8 meters (95% CI, 27.5-54.1; p<0.001) from baseline at week 24, the study’s primary endpoint.

In addition, sotatercept demonstrated statistically significant and clinically meaningful improvements in eight of nine secondary outcome measures, including improvements in WHO functional class (WHO FC) and pulmonary vascular resistance (PVR). Sotatercept reduced the risk of clinical worsening or death by 84% compared to placebo with a median follow-up of 32.7 weeks (HR=0.16 [95% CI, 0.08-0.35]; p<0.001). The safety profile of sotatercept was generally consistent with that observed in previous studies with sotatercept. These data were presented today at the American College of Cardiology’s 72^nd Annual Scientific Session together with World Heart Federation’s World Congress of Cardiology and simultaneously published in The New England Journal of Medicine.

“PAH is a rare, rapidly progressive, debilitating and ultimately life-threatening condition with a five-year mortality rate of 43 percent,” said Dr. Marius Hoeper, Hannover Medical School, Germany, and lead investigator. “Sotatercept demonstrated profound improvements across the primary endpoint of six-minute walk distance and multiple secondary endpoints, including improvements in WHO functional class and pulmonary vascular resistance. These landmark results show the potential of sotatercept and the approach of targeting cellular signaling associated with vascular hyperproliferation and pathological remodeling for the treatment of PAH.”

“The results from the Phase 3 STELLAR trial are immensely important to physicians and patients and highlight the critical role sotatercept may play in improving exercise capacity and other meaningful clinical outcome measures for patients with PAH,” said Dr. Dean Y. Li, president, MSD Research Laboratories. “These findings are compelling given the profound reduction in the risk of clinical worsening or death in patients treated with sotatercept on top of background therapy. We look forward to discussing these pivotal data with health authorities and are working with urgency to bring this potential new treatment option to patients.”

STELLAR is the first Phase 3 study to evaluate the efficacy of an activin signaling inhibitor added to background therapy in adults with PAH. Key findings from secondary endpoints included:

The proportion of patients who achieved multicomponent improvement at week 24 (defined as improvement in 6MWD, improvement in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and either improvement in WHO FC or maintenance of WHO FC II) was significantly greater with sotatercept versus placebo (38.9% [n=63/163] versus 10.1% [n=16/160]; p<0.001).
Sotatercept demonstrated a statistically significant reduction of -234.6 dyn·sec·cm⁻⁵ (95% CI, -288.4 to -180.8; p<0.001) from baseline at week 24 in PVR – a calculation of pulmonary artery pressure, pulmonary artery wedge pressure and cardiac output – versus placebo.
Sotatercept demonstrated a statistically significant reduction of -441.6 (95% CI, -573.5 to -309.6; p<0.001) from baseline at week 24 in NT-proBNP levels versus placebo.
Patients receiving sotatercept were significantly more likely to improve and maintain WHO FC at week 24 versus placebo. 29.4% (n=48/163) of patients in the sotatercept group improved in WHO FC compared to 13.8% (n=22/160) in the placebo group (p<0.001).
Sotatercept significantly reduced events associated with clinical worsening (defined by death of any cause or specified non-fatal clinical worsening events). With a median follow-up of 32.7 weeks, 9 of 163 patients in the sotatercept group died or experienced a clinical worsening event versus 42 of 160 patients in the placebo group (HR=0.16 [95% CI, 0.08 to 0.35]; p<0.001).
A significantly greater proportion of patients treated with sotatercept achieved or maintained a low French risk score (attaining or maintaining all three low-risk criteria: WHO functional class I or II, 6-minute walk distance > 440 meters, and NT-proBNP level < 300 pg per milliliter) versus placebo (39.5% [n=64/163] versus 18.2% [n=29/160]; p<0.001).
In patient-reported outcomes using the PAH-SYMPACT^® questionnaire, the average scores for Physical Impacts (change from baseline: -0.26 [95% CI, -0.49 to -0.04]; p=0.010) and Cardiopulmonary Symptoms (change from baseline: -0.13 [95% CI, -0.26 to -0.01]; p=0.028) were significantly reduced in patients treated with sotatercept versus placebo. PAH-SYMPACT^® is a disease-specific patient-reported outcome instrument. Domain scores range from 0 to 4 with higher scores indicating greater severity of symptoms.
The average score for Cognitive/Emotional Impacts using PAH-SYMPACT^® was not significantly different between patients treated with sotatercept versus placebo (p=0.156).

Treatment-emergent adverse events (TEAEs) occurred in 90.8% of patients who received sotatercept versus 91.9% of patients who received placebo, while severe TEAEs were observed in 12.9% versus 18.1% of patients, respectively. Adverse events that occurred more frequently with sotatercept versus placebo were bleeding events, telangiectasia, increased hemoglobin levels, thrombocytopenia, increased blood pressure, and dizziness.

Study design and additional data from the STELLAR trial

STELLAR (NCT04576988) was a pivotal Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the safety and efficacy of sotatercept in adult patients with PAH (WHO Group 1) being treated with background therapy with WHO Functional Class (FC) II or III. The primary endpoint of the study was exercise capacity, as measured by change from baseline in week 24 6MWD. Nine secondary endpoints, tested hierarchically in the following order, were multicomponent improvement, change in PVR, NT-proBNP level, improvement in WHO FC, time to clinical worsening or death, French risk score, and the PAH-SYMPACT^®Physical Impacts, Cardiopulmonary Symptoms and Cognitive/Emotional Impacts domain scores; all assessed at week 24 except clinical worsening, which was assessed when the last patient completed the week 24 visit.

The study enrolled a total of 323 participants who were randomized to receive either sotatercept (n=163) once every 3 weeks at a dose of 0.3 mg/kg at visit 1 and a dose of 0.7 mg/kg thereafter or placebo (n=160) added to stable background PAH therapy. The study population characteristics were: mean [±SD] 47.9 ± 14.8 years of age; 89% white; 79% female; and average length of time since PAH diagnosis of 8.8 years. In total,198 of the randomized patients (61.3%) were receiving triple therapy and 129 patients (39.9%) were receiving prostacyclin infusion therapy. Demographic and baseline characteristics were similar between the sotatercept and placebo groups.

The safety profile of sotatercept was generally consistent with that observed in the Phase 2 PULSAR trial. Seven patients (4.4%) in the placebo group and two patients (1.2%) in the sotatercept group died during the study through the data cutoff date.

About pulmonary arterial hypertension (PAH)

Pulmonary arterial hypertension (PAH) is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%.

About sotatercept

Sotatercept is an investigational, potential first-in-class activin signaling inhibitor biologic being studied for the treatment of PAH (WHO Group 1). PAH is a rare disease caused, in part, by hyperproliferation of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. In pre-clinical models, sotatercept has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.

Sotatercept has been granted Breakthrough Therapy Designation and Orphan Drug designation by the U.S. Food and Drug Administration (FDA), as well as Priority Medicines designation and Orphan Drug designation by the European Medicines Agency for the treatment of PAH. MSD acquired exclusive rights to sotatercept in the pulmonary hypertension field through the acquisition of Acceleron Pharma Inc. Sotatercept is the subject of a licensing agreement with Bristol Myers Squibb.

About MSD

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MSD’s MK-0616, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Patients with Hypercholesterolemia in Phase 2b Study

MK-0616 was generally well tolerated and reduced LDL-C across all dose levels compared to placebo

MSD plans to start Phase 3 pivotal study in the second half of 2023

RAHWAY, N.J., March 6, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK)today announced results from the Phase 2b clinical trial evaluating MK-0616, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in adults with hypercholesterolemia. The primary objective of the study was to evaluate the percent change in low density lipoprotein cholesterol (LDL-C) from baseline to week 8 for 4 doses of MK-0616 (6, 12, 18 and 30 mg) versus placebo. At week 8, all doses of MK-0616 significantly reduced LDL-C compared to placebo and the placebo-adjusted reduction from baseline ranged from 41.2% (6 mg, CI 95%, -47.8 to -34.7; p <0.001) to 60.9% (30 mg, 95% CI, -67.6 to -54.3; p<0.001). MK-0616 was generally well-tolerated at all 4 doses studied. These data were presented today at the American College of Cardiology’s 72^nd Annual Scientific Session together with World Congress of Cardiology (ACC.23/WCC) and simultaneously published in the Journal of The American College of Cardiology.

Inhibition of PCSK9 increases the removal of LDL-C from the bloodstream. MK-0616 is a macrocyclic peptide and is designed to lower LDL-C via the same biological mechanism as currently approved injectable PCSK9 inhibitors, but in a daily pill form. High LDL-C, if left untreated, can lead to a high risk of atherosclerotic cardiovascular disease (ASCVD) events, such as heart attacks and strokes.

“Despite widely available statin treatments, millions of patients are still not able to lower their cholesterol to the guideline-recommended levels and as a result are at increased risk for serious cardiovascular complications associated with atherosclerosis,” said Dr. Christie M. Ballantyne, principal investigator of the study and Professor of Medicine at Baylor College of Medicine. “Currently available PCSK9 inhibitors are effective tools to treat hypercholesterolemia but must be administered by injection. With these promising data showing that MK-0616 reduced LDL-C levels by up to 60.9%, MK-0616 should be further studied for its potential as a daily oral medicine.”

“These data reinforce our confidence that MK-0616 could become the first oral PCSK9 inhibitor, with the potential to change the way patients with hypercholesterolemia who need additional LDL-C reduction are treated. This may allow many more patients to reach their LDL-C treatment goals,” said Dr. Joerg Koglin, vice president, global clinical development, MSD Research Laboratories. “We look forward to advancing this program into Phase 3 development in the second half of this year.”

Additional data from the Phase 2b Study for MK-0616 (MK-0616-008)

MK-0616-008 (NCT05261126) was a randomized, double-blind, placebo-controlled, multi-center Phase 2b trial designed to evaluate the efficacy and safety of MK-0616 administered daily compared to placebo in adult participants with hypercholesterolemia and a broad spectrum of ASCVD risk. Participants were receiving a range of lipid-lowering therapies from no statin to high-intensity statin. The primary efficacy endpoint was the percent change in LDL-C from baseline to week 8. Supportive secondary endpoints (not multiplicity controlled) were percent change in apolipoprotein B-100 (ApoB) and in non-high-density lipoprotein-C (non-HDL-C) from baseline to week 8, and the proportion of participants who achieved protocol-defined LDL-C goals at week 8.

In total, 381 participants from age 18-80 with hypercholesterolemia with a moderate to high risk of atherosclerotic cardiovascular disease were randomized 1:1:1:1:1 to receive MK-0616 at a dose of 6 mg (n=77), 12 mg (n=76), 18 mg (n=76), or 30 mg (n=76) or placebo (n=76) once daily. The study population consisted of 49% female, 66% White, 17% Asian and 6% Black/African American, and 40% Latino or Hispanic.

At week 8, all doses of MK-0616 significantly reduced LDL-C compared to placebo and the results were generally consistent across the prespecified subgroups. The LDL-C placebo-adjusted reduction from baseline were as follows for each of the four doses studied (p<0.001 for all doses): 6 mg, 41.2% (95% CI, -47.8, -34.7), 12 mg, 55.7% (95% CI, -62.3, -49.1), 18 mg, 59.1% (95% CI, -65.7, -52.5), and 30 mg, 60.9% (95% CI, -67.6, -54.3). Near-complete efficacy was achieved by week 2, with the effect persisting over the eight-week treatment period. At week 8, improvements in secondary endpoints were also observed for all MK-0616 dose arms: ApoB levels were reduced by 32.8% (6 mg) to 51.8% (30 mg), non-HDL-C levels were reduced by 35.9% (6 mg) to 55.8% (30 mg), and protocol-defined LDL-C goals were achieved by 80.5% (6 mg) to 90.8% of participants (30 mg) versus 9.3% on placebo.

MK-0616 was generally well-tolerated with no overall trends across treatment groups in discontinuation rates or adverse events at week 16. No serious adverse events that were considered by the investigator to be related to treatment with MK-0616 were reported.

About PCSK9 and MK-0616

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of LDL receptors, which are responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 prevents the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

Discovered and developed by MSD, MK-0616 is an investigational, potentially first oral PCSK9 inhibitor designed to lower low density lipoprotein (LDL) cholesterol. MK-0616 is a macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

About Hypercholesterolemia

Hypercholesterolemia, a disorder in which there are elevated LDL-C levels in the blood, affects approximately 73 million adults in the U.S. It is a major risk factor associated with ASCVD, which is the leading cause of death in the U.S. and globally. Despite adjusting diet and taking statin therapies, many patients with hypercholesterolemia are still not reaching their LDL-C lowering goals as recommended by guidelines.

MSD’s Focus on Cardiovascular and Pulmonary Disease

Advancements in the treatment of cardiovascular disease can make a critical difference for patients around the world. At MSD, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally.

Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.msdclinicaltrials.com/.

About MSD

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MSD Opens Enrollment in New Phase 3 Clinical Trials with Investigational Once-Daily Islatravir in Combination with Doravirine for Treatment of HIV-1 Infection

Islatravir and other HIV data presented at CROI 2023

RAHWAY, N.J., Feb. 22, 2023 – MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK) announced today that the company has opened enrollment in its new Phase 3 clinical program with investigational once-daily islatravir 0.25 mg in combination with doravirine 100 mg (DOR/ISL) for the treatment of HIV-1 infection.

“Our extensive efficacy and safety analyses from the islatravir clinical program over the past year provided critical information to shape our research going forward,” said Todd Correll, executive director, DOR/ISL product development team lead, MSD Research Laboratories. “We believe islatravir in combination with doravirine has the potential to help make a difference for people living with HIV and are excited to open enrollment in our new Phase 3 clinical trials.”

Two new Phase 3 studies began enrolling participants this month:

MK-8591A-051 – A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy
MK-8591A-052 – A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

The following new Phase 3 studies are expected to begin enrollment in March:

MK-8591A-P053 – A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in HIV-1 Infected Treatment-Naïve Participants
MK-8591A-P054 – A Phase 3 Open-label Clinical Study of Doravirine/Islatravir (DOR/ISL [100 mg/0.25 mg]) Once-Daily for the Treatment of HIV-1 Infection in Participants Who Previously Received DOR/ISL (100 mg/0.75 mg) Once-Daily in a Phase 3 Clinical Study
- Certain study participants currently enrolled in prior DOR/ISL studies (Protocols 018, 020 and 033), which evaluated once-daily DOR/ISL 100/0.75 mg in treatment-naïve and virologically suppressed participants, will have the option of transitioning to study P054 evaluating once-daily DOR/ISL 100/0.25 mg as a potential fixed-dose combination, two-drug regimen.

Select MSD abstracts for islatravir at the Conference on Retroviruses and Opportunistic Infections (CROI) 2023 include:

Switch to DOR/ISL (100/0.75MG) QD From B/F/TAF: Week 48 Results From a Phase 3 Trial. Late-breaker oral presentation: 197. Mills, A, et al.
Switch to DOR/ISL (100/0.75MG) QD: Week 48 Results From An Open-label Phase 3 Trial. Late-breaker oral presentation: 196. Molina, J-M, et al.
Effect of Islatravir on Total Lymphocyte and Lymphocyte Subset Counts. Oral presentation: 192. Squires, K, et al.
Modeling To Optimize Islatravir QW Dose in HIV Virologically Suppressed PWH. Late-breaker poster: 497. Vargo, R, et al.

For more information, including details around the virtual programming, please visit the CROI 2023 website.

MSD’s Commitment to HIV

For more than 35 years, MSD has been committed to scientific research and discovery (R&D) in HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We remain committed to working hand-in-hand with our partners in the global HIV community to address the complex challenges that impede progress toward ending the epidemic.

About MSD

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2021 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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MSD Collaborator Instituto Butantan Announces Results from Its Phase 3 Vaccine Candidate Trial for the Prevention of Dengue Disease

RAHWAY, N.J., Dec. 16, 2022 – At MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK), we are highly encouraged by the tremendous progress scientists and clinicians at the Instituto Butantan have made in developing their single dose dengue disease vaccine candidate. We are working with Instituto Butantan to conduct a detailed analysis of these results in order to determine next steps for our own dengue vaccine candidate (V181).

Instituto Butantan’s announcement represents an important clinical research milestone for the global health community. Both MSD and Instituto Butantan’s investigational vaccines are derived from materials licensed from the U.S. National Institutes of Health (NIH) and both institutions are evaluating formulations analogous to the NIH TV003 formulation. Under the collaboration agreement announced in December 2018, MSD and Instituto Butantan are sharing clinical data and other learnings from their respective dengue vaccine development programs.

This collaboration is an example of how MSD is engaging the global public health community to develop vaccines for important diseases primarily affecting tropical and subtropical regions of the world.

About dengue

Dengue is one of the fastest growing mosquito-borne diseases that affects not just the health but often the economic stability of people across the globe. It is a leading cause of serious and sometimes debilitating illness in tropical and subtropical countries.¹ With approximately half of the world’s population, or four billion people, at risk for dengue disease, dengue is a critical public health challenge. Globally, 400 million dengue infections occur annually, according to the WHO², with 50-100 million infections being symptomatic.^3,4 While the majority of infections are uncomplicated, serious illness caused by dengue can be severe and lead to death⁵ (~500,000 cases per year are severe enough to require hospitalization and ~2.5% of severely affected individuals may die⁶). Mild dengue fever is characterized by a high fever, rash, and muscle and joint pain. A severe form of dengue fever, (dengue hemorrhagic fever) can cause severe bleeding, a sudden drop in blood pressure and death.⁷

About MSD

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¹WHO | Dengue and severe dengue. Published online 2022. Accessed November 28, 2022. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue

²WHO | Dengue and severe dengue. Published online 2022. Accessed November 28, 2022. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue

³Russell KL, Rupp RE, Morales-Ramirez JO, et al. A phase I randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and immunogenicity of a live-attenuated quadrivalent dengue vaccine in flavivirus-naïve and flavivirus-experienced healthy adults. Hum Vaccin Immunother. Published online 2022:1-12. doi:10.1080/21645515.2022.2046960

⁴Messina JP, Brady OJ, Golding N, et al. The current and future global distribution and population at risk of dengue. Nat Microbiol. 2019;4(9):1508-1515. doi:10.1038/s41564-019-0476-8

⁵WHO | Dengue and severe dengue. Published online 2022. Accessed November 28, 2022. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue

⁶WHO | Dengue and severe dengue. Published online 2021. Accessed June 6, 2022. https://apps.who.int/mediacentre/factsheets/fs117/en/index.html

⁷Mayo Clinic | Dengue fever. Published online 2022. Accessed November 28, 2022. https://www.mayoclinic.org/diseases-conditions/dengue-fever/symptoms-causes/syc-20353078#:~:text=The%20severe%20form%20of%20dengue,pressure%20(shock)%20and%20death.

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